The human corneal epithelium covers the front of the cornea and protects the eye (FIG. 1). It is made up of epithelial tissue and normally has five to six cell layers.1 Conical epithelium is a self-renewing tissue. It's highly active and a complete turnover takes place in approximately a week.2 Corneal epithelium is able to alter its thickness to mask sub-epithelial stromal irregularities and maintain a smooth optical surface of the eye.3 In diseases such as keratoconus, the thickness of the epithelium becomes altered to reduce corneal surface irregularity. Therefore, the presence of an irregular stroma may be less measurable by frontal surface corneal topography. Analyzing the corneal epithelium and stroma thickness and shape separately can facilitate the detection of the disease in its early stage.
On the other hand, corneal epithelium contributes to the total corneal power due to its thickness profile and the difference in refractive index between epithelium and stroma (1.401 vs 1.380).4 In laser corneal surgeries, the common way to perform photorefractive keratectomy (PRK) or phototherapeutic keratectomy (PTK) is to remove the epithelium first. Therefore, it is useful to measure the corneal topography and power under the epithelium for the purpose of planning PRK/PTK surgeries. Moreover, epithelial smoothing following laser keratorefractive surgery such as PRK or LASIK has been modeled mathematically.3 What is still needed is the capability to map the corneal epithelium. This can aid in the understanding of epithelial thickness modulation after ablation. Eventually this knowledge may help minimize the regression after surgery and the aberration induced by the surgery.
To this end, different methods, such as optical coherence tomography (OCT), confocal microscopy and optical pachymetry and confocal microscopy have been used to measure corneal epithelial thickness. Many of these studies measured average central epithelium thickness. Some studies used OCT or confocal microscopy to measure peripheral epithelium thickness, but the number of points measured in the periphery was limited5-7 and the measurement was very time consuming.5 Ultrahigh frequency ultrasound imaging (Artemis by Ultralink, Inc.) can also map corneal epithelium and stromal thickness.8-13 However, it requires immersing the eye in a fluid bath because ultrasound cannot pass through air. The inconvenience and discomfort associated with the fluid bath makes it unsuitable for clinical applications.
Optical coherence tomography (OCT) is a non-contact imaging technique based on principles of low-coherence interferometry.14 Its high axial resolution allows better delineation of the anterior and posterior surfaces of the cornea. Time-domain anterior segment OCT systems capable of generating pachymetry (corneal thickness) maps have been reported.15,16 However, time-domain OCT still suffers from slow speed which makes it susceptible to eye movements during image acquisition.
Recently, a newer generation of OCT known as Fourier-domain OCT (FD-OCT) has been made available. This new generation of OCT has acquisition speeds 10-100 times faster than time-domain OCT systems.17-19 The very high scan speed may minimize the effect of eye movement during data acquisition while obtain dense sample points over the cornea. Although promising, acquiring and analyzing data using FD-OCT is not trivial. No known method of using FD-OCT to generate corneal epithelial and/or stromal map has heretofore been reported.
In view of the above, there still exists a need for a fast, reliable, and convenient method that is suitable for clinical measurement of corneal epithelium and/or stromal properties such as thickness and refractive power. There are many clinical utilities for such measurements. One particular application that can benefit from such a method is keratoconus.
Keratoconus is an important contraindication for refractive surgeries such as LASIK. Undetected corneal ectatic disorders can result in accelerated, progressive keratoectasia and produces poor vision that cannot be corrected with spectacles.
The National Eye Institute reports that keratoconus is the most common corneal dystrophy in the United. States, affecting approximately 1 in 2,000 Americans, but some reports place the figure as high as 1 in 500. In keratoconus, the normally round basketball-shaped cornea progressively thins and becomes football shaped causing a cone-like bulge to develop, and slight blurring and distortion of vision and increased sensitivity to light in its earliest stages. In later stages, it causes decreased visual acuity and significant visual impairment, which makes simple tasks, like driving, watching TV or reading a book nearly impossible.
Moderate to advanced keratoconus is easily recognizable by several distinctive clinical features, but the diagnosis of early stage keratoconus can be very challenging.22 Surgeons learned to better recognize the early stage keratoconus (referred to as forme fruste keratoconus or FFK in medical literature) on corneal topography.23,24 However, topography does not screen out all eyes at risk. Topography measures only anterior topographic distortion. But keratoconus is also characterized by posterior topographic steepening, focal corneal thinning, and focal epithelial thinning. Detecting these changes with OCT could improve risk assessment and thus reduce the incidence of post-LASIK ectasia.